Objective To compare patients with autopsy-confirmed Alzheimer’s disease (AD #14) and Dementia with Lewy bodies GSK1324726A (DLB) around the frequency of actions related to frontal systems dysfunction and the association of these actions with dementia severity. apathy disinhibition and executive dysfunction by a knowledgeable informant. Results A two-way analysis of variance with the FrSBe total as the dependent variable revealed a significant MMSE by diagnosis conversation (F(1 53 p=.004). Mean LRCH1 FrSBe total for AD patients showed significant impairment across the range of dementia severity while it was relatively preserved for DLB patients in early stage of disease. The conversation term showed the same pattern for the executive dysfunction (F(1 53 p=.008) disinhibition (F(1 53 p=.031) and apathy (F(1 53 p=.003) subscales. Conclusions While frontal behavioral symptoms in AD patients were present regardless of stage of dementia DLB patients showed significant frontal dysfunction only in later stages. Results suggest that frontal subcortical circuits associated with actions assessed by the FrSBe are affected early in AD but not until later stages in DLB. Assessing specific behaviors related to frontal systems coupled with stage of cognitive decline may aid in clinical differentiation of AD and DLB. Keywords: Dementia with Lewy body Alzheimer’s disease Frontal systems Behavioral symptoms OBJECTIVE Dementia with Lewy body (DLB) is usually a neurodegenerative disorder accounting for roughly 10 to 15% of cases of dementia in the elderly (1). The neuropathological hallmarks of the disease are the presence of Lewy body predominantly in the temporal parietal and frontal cortices accompanied by degeneration of the nigrostriatal dopaminergic pathway. The disease is usually characterized clinically by progressive cognitive decline often with visual hallucinations parkinsonism and fluctuating alertness. Efforts to refine diagnostic criteria for DLB have been made (2). Nevertheless diagnostic sensitivity has remained stubbornly low because DLB shares features with other neurodegenerative conditions including Alzheimer’s disease (3). The discriminative value of behavioral symptoms of dementia for diagnosis of common neurodegenerative disorders however has been stressed (4). Previous studies have supported differences in the behavioral characteristics of DLB GSK1324726A and AD. Compared to AD DLB has been characterized by a relatively high prevalence of hallucinations delusions stress anhedonia and loss of energy occurring in earlier stages of disease (5) based on the Mini-Mental State Examination (MMSE) (6). The retrospective nature of these findings limited the inferences that could be made; however comparable results were obtained from prospective studies of neuropsychiatric changes in personality characteristics (7 GSK1324726A 8 arising from DLB. Around the Blessed Dementia Level (9) (BDS) caregivers of DLB patients were more likely than AD caregivers to endorse actions such as diminished emotional responsiveness apathy purposeless hyperactivity and relinquished hobbies subsumed under a factor of “passivity” despite noting comparable levels of irritability and GSK1324726A disinhibition (8). The design of the study could not address the timeline associated with the development of passivity in the DLB patients because the BDS scoring system does not allow for quantifiable ratings of behavioral switch. A series of studies (7 10 examined the relationship between DLB and behaviors common to frontal lobe damage. Using a measure GSK1324726A previously shown to differentiate frontotemporal dementia from AD [Middelheim Frontality Score (MFS) (11)] investigators found no difference in clinically diagnosed DLB and AD patients in the frequency of frontal lobe actions when divided by dementia severity. Engelborghs et al. (10) found that for both the DLB and AD groups there was a negative correlation between the MFS and MMSE total score. Aries et al. (7) found that for both diagnostic groups with dementia stage based on the Global Deterioration Level (12) the group with severe dementia had more frontal lobe actions around the 10-item MFS than the group with moderate dementia; however they found no significant differences between moderate and moderate stages. The MFS samples a variety of behaviors that include disinhibition as well as aspontaneity and emotional bluntness characteristics often associated with apathy. GSK1324726A The Aries et al. study (7) however.